Lymphokine preparations of human or murine origin contain a low molecular weight protein, TMIF, that can reversibly inhibit the migration of a variety of tumor cells, obtained from serially passaged animal tumors as well as from spontaneous human neoplasms. These preparations can also inhibit the binding of tumor cells to endothelium. It is not yet known whether the responsible factor for this latter activity (TBIF) is distinct from TMIF. These factors are not cytotoxic. The existence of these activities, appearing within a narrow molecular weight range (5,00-10,000 daltons) different from that of other known lymphokines, lead to the hypothesis that there is a distinct class of lymphokine mediators with the common feature of influencing functional properties of tumor cells. Since these functions are those that are involved in the expression of malignant potential, these mediators could have therapeutic application. They can be partially purified by simple sizing procedures to exclude other categories of lymphokines, as well as small molecular weight agents such as prostaglandins. We now propose to purify these factors to homogeneity by physicochemical techniques such as HPLC and FPLC, as well as immunoaffinity chromatography. Purified TMIF and TBIF, monoclonal antibodies prepared against these factors, and monoclonal antibodies against the tumor cell surface binding site responsible for the attachment of that cell to endothelium will be used to study the mechanisms by which these lymphokines exert their effects, with special attention to their interaction with surface receptors on their target cells. Although the bulk of these studies involve in vitro effects, an attempt will be made to demonstrate that TMIF and/or TBIF are effective in vivo as well, utilizing a tumor arrest model.